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New Insights in Natural Bioactive Compounds 2.0
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New Insights in Natural Bioactive Compounds 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 22101

Special Issue Editors

Prof. Dr. Letteria Minutoli

E-Mail Website
Guest Editor
Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
Interests: preclinical pharmacology; inflammation; oxidative stress; natural products; flavonoids; cannabinoids
Special Issues, Collections and Topics in MDPI journals
Dr. Giovanni Pallio

E-Mail Website
Guest Editor
Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, Via C. Valeria, 98125 Messina, Italy
Interests: preclinical pharmacology; inflammation; oxidative stress; natural products; flavonoids; cannabinoids
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

This Special Issue is a continuation of our previous successful Special Issue “New Insights in Natural Bioactive Compounds”.

Natural bioactive compounds are small molecules produced naturally by several plants, including primary and secondary metabolites. Natural bioactive compounds have a wide range of possible applications and can be useful in the treatment and management of various kinds of human diseases due to their outstanding biological properties. Moreover, bioactive compounds and pharmaceuticals derived from natural products have received increasing attention due to their considerable benefits for human health. This Special Issue will shape the future research direction of important natural products, as well as related bioactives. Our purpose is to feature high-quality, advanced research and knowledge contributed by various research groups working on natural products from all around the world. We cordially invite authors to contribute original articles, as well as review papers on the functional and medicinal properties of natural products for preventing and managing human diseases.

Prof. Dr. Letteria Minutoli
Dr. Giovanni Pallio
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • inflammation
  • cytokines
  • ROS
  • oxidative stress
  • natural products
  • flavonoids
  • cannabinoids

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Published Papers (17 papers)

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18 pages, 3755 KiB  
Article
Olive Pomace Extract Contains Low Molecular Weight Peptides and Possesses ACE Inhibitory Activity
by Eduardo López-Huertas, Jose Rubí-Villegas, Lourdes Sánchez-Moreno and Rosa Nieto
Int. J. Mol. Sci. 2024, 25(7), 3962; https://doi.org/10.3390/ijms25073962 - 02 Apr 2024
Viewed by 452
Abstract
The aim of the present study was to determine the ACE inhibitory activity of aqueous extracts of olive pomace and to understand whether they represent a good source of bioactive LMW peptides for nutritional and pharmacological applications. We produced a water extract from [...] Read more.
The aim of the present study was to determine the ACE inhibitory activity of aqueous extracts of olive pomace and to understand whether they represent a good source of bioactive LMW peptides for nutritional and pharmacological applications. We produced a water extract from olive pomace (var. Picual) and obtained its low molecular weight (LMW) fraction (<3 kDa). The calculated yield of extraction was 100.2 ± 7.9 mg of LMW peptides per 100 g of olive pomace. The olive pomace LMW fraction possessed strong ACE inhibitory activity (IC50 = 3.57 ± 0.22 µg prot/mL). The LMW fraction (<3 kDa) was analysed by nanoscale liquid chromatography-Orbitrap coupled with tandem mass spectrometry and de novo sequencing. Thirty new peptides, containing between 7–17 amino acids and molecular masses ranging 778–1354 Da, were identified by the Peaks database algorithm using the available Olea europaea (cv. Farga) genome database. Ten new peptides were also identified by Peaks de novo sequencing. The protein sources of twelve peptides detected in the database by Peaks DB were identified by BLAST search. The ACE inhibitory activity of the identified peptides was predicted by BIOPEP software. We conclude that olive pomace possesses ACE inhibitory activity and contains low molecular weight peptides with (predicted) biological activity. Olive pomace may represent a good source of peptides for nutritional and pharmaceutical applications. In our study, it has been shown that olive pomace possesses ACE inhibitory activity and contains low molecular weight peptides with (predicted) biological activity. Olive pomace may represent a good source of peptides for nutritional and pharmaceutical applications. More research is needed in order to identify the in vivo effects of olive pomace bioactive peptides. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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15 pages, 3186 KiB  
Article
Ethyl Acetate Fraction from a Catalpa ovata G. Don Extract Inhibits ɑ-MSH-Induced Melanogenesis through the cAMP/CREB Pathway
by Yon-Suk Kim, Eun-Bin Lee, Ye-Ji Yu, Ga-Won Kim, Woo-Jung Kim and Dong-Kug Choi
Int. J. Mol. Sci. 2024, 25(1), 151; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25010151 - 21 Dec 2023
Viewed by 730
Abstract
The whitening effect of reducing skin pigmentation is one of the most important goals of cosmetics. The purpose of this study was to determine whether Catalpa ovata extract and its fractions have potential as natural skin-lightening agents. Initially, we screened various fractions of [...] Read more.
The whitening effect of reducing skin pigmentation is one of the most important goals of cosmetics. The purpose of this study was to determine whether Catalpa ovata extract and its fractions have potential as natural skin-lightening agents. Initially, we screened various fractions of Catalpa ovata extract using an in vitro antioxidant assay. Then, the inhibitory effects of C. ovata extract and its fraction on melanogenesis and the related mechanisms were investigated in B16F1 melanoma cells. The results showed that the ethyl acetate fraction (EF) from C. ovata extract markedly inhibited melanin synthesis in a dose-dependent manner at non-toxic concentrations. Furthermore, EF downregulated both the protein and mRNA levels of tyrosinase, which is a specific enzyme that catalyzes the conversion of tyrosine into melanin. We also found that EF decreased the microphthalmia-associated transcription factor (MITF) at the protein and mRNA levels. EF increased the phosphorylation of ERK and suppressed the phosphorylation of JNK and p38 in ɑ-MSH-induced B16F1 cells. These results indicate that EF can regulate the MAPK pathway. In addition, EF has an anti-melanogenic effect via the downregulation of intracellular cyclic-AMP (cAMP). Nineteen major compounds of EF were identified using LC-MS/MS. Taken together, these results suggest that EF may be a potential anti-melanogenic agent for use in skin-whitening cosmetics and in topical treatments for hyperpigmentation disorders. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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14 pages, 2259 KiB  
Article
Isolation of Pro-Osteogenic Compounds from Euptelea polyandra That Reciprocally Regulate Osteoblast and Osteoclast Differentiation
by Ryuichiro Suzuki, Yoshiaki Shirataki, Akito Tomomura, Kenjiro Bandow, Hiroshi Sakagami and Mineko Tomomura
Int. J. Mol. Sci. 2023, 24(24), 17479; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242417479 - 14 Dec 2023
Viewed by 907
Abstract
Plants contain a large number of small-molecule compounds that are useful for targeting human health and in drug discovery. Healthy bone metabolism depends on the balance between bone-forming osteoblast activity and bone-resorbing osteoclast activity. In an ongoing study searching for 22 plant extracts [...] Read more.
Plants contain a large number of small-molecule compounds that are useful for targeting human health and in drug discovery. Healthy bone metabolism depends on the balance between bone-forming osteoblast activity and bone-resorbing osteoclast activity. In an ongoing study searching for 22 plant extracts effective against osteoporosis, we found that the crude extract of Euptelea polyandra Sieb. et Zucc (E. polyandra) had osteogenic bioactivity. In this study, we isolated two compounds, isoquercitrin (1) and astragalin (2), responsible for osteogenic bioactivity in osteoblastic MC3T3-E1 cells from the leaf of E. polyandra using column chromatography and the spectroscopic technique. This is the first report to isolate astragalin from E. polyandra. Compounds (1) and (2) promoted osteoblast differentiation by increasing alkaline phosphatase (ALP) activity and alizarin red S stain-positive calcium deposition, while simultaneously suppressing tartrate-resistant acid phosphatase (TRAP)-positive osteoclast differentiation in RAW264.7 cells at non-cytotoxic concentrations. Isoquercitrin (1) and astragalin (2) increased the expression of osteoblastic differentiation genes, Osterix, ALP, and Osteoprotegerin in the MC3T3-E1 cells, while suppressing osteoclast differentiation genes, TRAP, Cathepsin K, and MMP 9 in the RAW264.7 cells. These compounds may be ideal targets for the treatment of osteoporosis due to their dual function of promoting bone formation and inhibiting bone resorption. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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23 pages, 8135 KiB  
Article
Development of New Dermato-Cosmetic Therapeutic Formulas with Extracts of Vinca minor L. Plants from the Dobrogea Region
by Ana-Maria Neculai, Gabriela Stanciu, Anca Cristina Lepădatu, Luiza-Madălina Cima, Magdalena Mititelu and Sorinel Marius Neacșu
Int. J. Mol. Sci. 2023, 24(22), 16234; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242216234 - 12 Nov 2023
Cited by 1 | Viewed by 872
Abstract
A new trend in the use of indole alkaloids from natural products is the preparation of topical pharmaceutical formulations with applications in the field of regenerative medicine. These formulations can be characterized through the ease of administration, the proven healing action of indole [...] Read more.
A new trend in the use of indole alkaloids from natural products is the preparation of topical pharmaceutical formulations with applications in the field of regenerative medicine. These formulations can be characterized through the ease of administration, the proven healing action of indole alkaloids, the protection of skin lesions, and the assurance of oxygen permeability. Based on the numerous benefits that indole compounds extracted from the Vinca minor plant show externally, the purpose of this study was to develop new semi-solid biocomposites for topical application obtained from hydroalcoholic macerates of 40%, 70%, and 96% concentrations from the stems and leaves of the Vinca minor L. plant from the Dobrogea area. A total of 12 pharmaceutical formulations (named P1–P12) were prepared for which the physicochemical properties, pH, thermal stability, spreading capacity, and rheological behavior were determined. The optimal formulas with antioxidant and antimicrobial capacity were evaluated and determined (P3, P4, P9, and P10). Antioxidant activity was elicited using the photochemiluminescence method. The microorganisms used for the evaluation of antimicrobial activity were Gram-positive Staphylococcus aureus (ATCC 25923), Gram-negative Escherichia coli (ATCC 25922), and a fungal species, Candida albicans (ATCC 900288). The study of the rheological profile for the obtained composites revealed Newtonian, pseudoplastic, and thixotropic fluid behaviors. Following determinations using the photochemiluminescence method, the best antioxidant activity was obtained in the P3 and P9 preparations. The results of the antimicrobial analysis confirmed that both the leaves and the stems of the Vinca minor plant represent a valuable source of antibacterial substances, and the biocomposites analyzed may represent an alternative in the realization of new pharmaceutical preparations with topical applications based on hydroalcoholic macerates obtained from the Vinca minor plant. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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14 pages, 4027 KiB  
Article
Investigation of the Membrane Localization and Interaction of Selected Flavonoids by NMR and FTIR Spectroscopy
by Justyna Kapral-Piotrowska, Jakub W. Strawa, Katarzyna Jakimiuk, Adrian Wiater, Michał Tomczyk, Wiesław I. Gruszecki and Bożena Pawlikowska-Pawlęga
Int. J. Mol. Sci. 2023, 24(20), 15275; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242015275 - 17 Oct 2023
Cited by 1 | Viewed by 701
Abstract
In this report, we discuss the effects of undescribed flavone derivatives, HZ4 and SP9, newly isolated from the aerial parts of Hottonia palustris L. and Scleranthus perennis L. on membranes. Interaction of flavonoids with lipid bilayers is important for medicinal applications. The experiments [...] Read more.
In this report, we discuss the effects of undescribed flavone derivatives, HZ4 and SP9, newly isolated from the aerial parts of Hottonia palustris L. and Scleranthus perennis L. on membranes. Interaction of flavonoids with lipid bilayers is important for medicinal applications. The experiments were performed with FTIR and NMR techniques on liposomes prepared from DPPC (dipalmitoylphosphatidylcholine) and EYPC (egg yolk phosphatidylcholine). The data showed that the examined polyphenols incorporate into the polar head group region of DPPC phospholipids at both 25 °C and 45 °C. At the lower temperature, a slight effect in the spectral region of the ester carbonyl group is observed. In contrast, at 45 °C, both compounds bring about the changes in the spectral regions attributed to antisymmetric and symmetric stretching vibrations of CH2 and CH3 moieties. Similarly, as in DPPC lipids, the tested compounds interact with the fingerprint region of the polar head groups of the EYPC lipids and cause its reorganization. The outcomes obtained by NMR analyses confirmed the localization of both flavonoids in the polar heads zone. Unraveled effects of HZ4 and SP9 in respect to lipid bilayers can partly determine their biological activities and are crucial for their usability in medicine as disease-preventing phytochemicals. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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16 pages, 1089 KiB  
Article
Innovative Integration of Arrayan (Luma apiculata) Extracts in Chitosan Coating for Fresh Strawberry Preservation
by Sergio Benavides and Wendy Franco
Int. J. Mol. Sci. 2023, 24(19), 14681; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241914681 - 28 Sep 2023
Cited by 1 | Viewed by 1366
Abstract
Strawberries are a rich source of vitamins and antioxidants, among other nutrients, but they are highly susceptible to mechanical injuries, dehydration, and microbial spoilage, and thus have a limited post-harvest shelf-life. Bioactive edible coatings have been studied to decrease or prevent these damages. [...] Read more.
Strawberries are a rich source of vitamins and antioxidants, among other nutrients, but they are highly susceptible to mechanical injuries, dehydration, and microbial spoilage, and thus have a limited post-harvest shelf-life. Bioactive edible coatings have been studied to decrease or prevent these damages. In this study, ethanolic extracts of Arrayan (Luma apiculata), a traditional berry from the south of Chile, were used to enrich a chitosan-based edible film and coat fresh strawberries. A long-term storage (10 °C) study was conducted to determine the strawberries’ weight loss, microbial stability, fruit firmness impact, and antioxidant activity. Later, a sensory panel was conducted to determine overall consumer acceptance. Our results show that the bioactive coating inhibited the growth of different pathogenic bacteria and spoilage yeast. In the stored strawberries, the weight loss was significantly lower when the bioactive coating was applied, and the samples’ firmness did not change significantly over time. Microbial growth in the treated strawberries was also lower than in the control ones. As expected, the antioxidant activity in the coated strawberries was higher because of the Arrayan extract, which has high antioxidant activity. Regarding sensory qualities, the covered strawberries did not show significant differences from the uncoated samples, with an overall acceptance of 7.64 on a 9-point scale. To our knowledge, this is the first time an edible coating enriched with Arrayan extracts has been reported as able to prevent strawberries’ decay and spoilage. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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16 pages, 5804 KiB  
Article
Mitigation of Dextran-Sodium-Sulfate-Induced Colitis in Mice through Oral Administration of Microbiome-Derived Inosine and Its Underlying Mechanisms
by Weiling Guo, Xin Tang, Qiuxiang Zhang, Jianxin Zhao, Bingyong Mao, Hao Zhang and Shumao Cui
Int. J. Mol. Sci. 2023, 24(18), 13852; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241813852 - 08 Sep 2023
Cited by 3 | Viewed by 1152
Abstract
Background: Colonic and serum inosine are significantly reduced in patients with inflammatory bowel disease (IBD). Methods: This study aimed to explore whether microbiome-derived inosine alleviates colitis and its underlying mechanisms. Results: An inosine intervention effectively improved the clinical signs in colitis mice, suppressed [...] Read more.
Background: Colonic and serum inosine are significantly reduced in patients with inflammatory bowel disease (IBD). Methods: This study aimed to explore whether microbiome-derived inosine alleviates colitis and its underlying mechanisms. Results: An inosine intervention effectively improved the clinical signs in colitis mice, suppressed inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β) by regulating the nuclear factor-kappa B (NF-κB) pathway, and elevated the activities of anti-oxidative enzymes (including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)) by regulating the nuclear factor erythroid-2 related factor 2 (Nrf2) pathway. Additionally, the inosine intervention significantly elevated the expression of tight junction proteins (ZO-1, occudin, and claudin-1) in mice with colitis. High-throughput sequencing revealed that the inosine intervention also prevented gut microbiota disorder by increasing the abundance of beneficial bacteria (Lachnospiraceae NK4A136 group, Romboutsia, Marvinbryantia, Clostridium sensu stricto 1, and Bifidobacterium) and reducing the abundance of harmful bacteria (Pseudomonas, Acinetobacter, and Tyzzerella) in mice with colitis. Conclusions: Inosine played a significant role in mitigating colitis-related intestinal barrier injury and could potentially be used for therapy in clinical practice. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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15 pages, 2298 KiB  
Article
Positive Effects of the Nutraceutical Association of Lycopene and Selenium in Experimental Varicocele
by Jose Freni, Giovanni Pallio, Herbert Ryan Marini, Antonio Micali, Natasha Irrera, Carmelo Romeo, Domenico Puzzolo, Federica Mannino, Letteria Minutoli, Igor Pirrotta, Alessandro Scarfone and Pietro Antonuccio
Int. J. Mol. Sci. 2023, 24(17), 13526; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241713526 - 31 Aug 2023
Cited by 2 | Viewed by 1836
Abstract
Many natural substances commonly found in healthy diets have been studied for their potential to reduce male infertility associated with varicocele. A positive role of selenium (Se) or lycopene alone was demonstrated in experimental varicocele, while no data are available on their association. [...] Read more.
Many natural substances commonly found in healthy diets have been studied for their potential to reduce male infertility associated with varicocele. A positive role of selenium (Se) or lycopene alone was demonstrated in experimental varicocele, while no data are available on their association. One group of male Sprague–Dawley rats was sham operated and daily treated with Se (3 mg/kg, i.p.), lycopene (1 mg/kg, i.p.), or their association. A second group underwent surgery to induce varicocele. Sham and half of the varicocele animals were sacrificed after twenty-eight days, while the residual animals were treated for one more month and then sacrificed. In varicocele animals, testosterone levels and testes weight were reduced, Hypoxia Inducible Factor-1α (HIF-1α) expression was absent in the tubules and increased in Leydig cells, caspare-3 was increased, seminiferous epithelium showed evident structural changes, and many apoptotic germ cells were demonstrated with TUNEL assay. The treatment with lycopene or Se alone significantly increased testis weight and testosterone levels, reduced apoptosis and caspase-3 expression, improved the tubular organization, decreased HIF-1α positivity of Leydig cells, and restored its tubular positivity. Lycopene or Se association showed a better influence on all biochemical and morphological parameters. Therefore, the nutraceutical association of lycopene plus Se might be considered a possible therapeutic tool, together with surgery, in the treatment of male infertility. However, long-term experimental and clinical studies are necessary to evaluate sperm quantity and quality. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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15 pages, 5964 KiB  
Article
Retinoic Acid Receptor β Loss in Hepatocytes Increases Steatosis and Elevates the Integrated Stress Response in Alcohol-Associated Liver Disease
by Marta Melis, Steven E. Trasino, Xiao-Han Tang, Andrew Rappa, Tuo Zhang, Lihui Qin and Lorraine J. Gudas
Int. J. Mol. Sci. 2023, 24(15), 12035; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241512035 - 27 Jul 2023
Viewed by 1048
Abstract
In alcohol-associated liver disease (ALD), hepatic reductions in vitamin A and perturbations in vitamin A metabolism are common. However, the roles that the vitamin A receptors, termed retinoic acid receptors (RARs), may have in preventing the pathophysiology of ALD remains unclear. Our prior [...] Read more.
In alcohol-associated liver disease (ALD), hepatic reductions in vitamin A and perturbations in vitamin A metabolism are common. However, the roles that the vitamin A receptors, termed retinoic acid receptors (RARs), may have in preventing the pathophysiology of ALD remains unclear. Our prior data indicate that a RARβ agonist limits the pathology of alcohol-related liver disease. Thus, we generated liver-specific AlbCre–RARβ knockout (BKO) mice and compared them to wild type (WT) mice in an early ALD model. Both strains showed similar blood ethanol concentrations and ETOH-metabolizing enzymes. However, the livers of pair-fed-BKO and ETOH-BKO mice developed higher levels of steatosis and triglycerides than pair-fed-WT and ETOH-WT mice. The increased hepatic steatosis observed in the pair-fed-BKO and ETOH-BKO mice was associated with higher lipid synthesis/trafficking transcripts and lower beta-oxidation transcripts. ETOH-BKO mice also exhibited a higher integrated stress response (ISR) signature, including higher transcript and protein levels of ATF4 and its target, 4-EBP1. In human hepatocytes (HepG2) that lack RARβ (RARβ-KO), ETOH treatments resulted in greater reactive oxygen species compared to their parental cells. Notably, even without ETOH, ATF4 and 4-EBP1 protein levels were higher in the RARβ-KO cells than in their parental cells. These 4-EBP1 increases were greatly attenuated in cultured ATF4-deficient and RARβ/ATF4-deficient HepG2, suggesting that RARβ is a crucial negative regulator of 4-EBP1 through ATF4 in cultured hepatocytes. Here, we identify RARβ as a negative regulator of lipid metabolism and cellular stress in ALD. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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17 pages, 4653 KiB  
Article
Inhibitory Effects of Polyphenol- and Flavonoid-Enriched Rice Seed Extract on Melanogenesis in Melan-a Cells via MAPK Signaling-Mediated MITF Downregulation
by Chaiwat Monmai, Jin-Suk Kim, Joong Hyoun Chin, Sanghyun Lee and So-Hyeon Baek
Int. J. Mol. Sci. 2023, 24(14), 11841; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241411841 - 24 Jul 2023
Cited by 3 | Viewed by 1299
Abstract
Melanin production is an important process that prevents the host skin from harmful ultraviolet radiation; however, an overproduction of melanin results in skin diseases. In the present study, we determined the antioxidative and anti-melanogenic activities of polyphenol- and flavonoid-enriched rice seed extracts in [...] Read more.
Melanin production is an important process that prevents the host skin from harmful ultraviolet radiation; however, an overproduction of melanin results in skin diseases. In the present study, we determined the antioxidative and anti-melanogenic activities of polyphenol- and flavonoid-enriched rice seed extracts in melan-a cells. The polyphenol and flavonoid content of Hopum (HP) and Sebok (SB) rice seed extracts was measured. The antioxidant capacity was determined using the ABTS radical scavenging method. SB contained high amounts of polyphenols and flavonoids, which significantly increased antioxidative activity compared with HP. Various concentrations of these extracts were evaluated in a cytotoxicity using melan-a cells. At 100 µg/mL, there was no significant difference for all treatments compared with untreated cells. Therefore, 100 µg/mL was selected as a concentration for the further experiments. SB significantly suppressed the phosphorylation/activation of p-38 MAPK, increased the expression of phosphorylated ERK 1/2 and Akt, and downregulated the microphthalmia-associated transcription factor (MITF). This resulted in decreased levels of tyrosinase and tyrosinase-related protein-1 and -2. These results indicate the potential of polyphenol- and flavonoid-enriched rice seed as a treatment for hyperpigmentation. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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17 pages, 4842 KiB  
Article
Possible Molecular Mechanisms Underlying the Decrease in the Antibacterial Activity of Protamine-like Proteins after Exposure of Mytilus galloprovincialis to Chromium and Mercury
by Carmela Marinaro, Gennaro Lettieri, Mariavittoria Verrillo, Michela Morelli, Federica Carraturo, Marco Guida and Marina Piscopo
Int. J. Mol. Sci. 2023, 24(11), 9345; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24119345 - 26 May 2023
Cited by 1 | Viewed by 839
Abstract
Natural bioactive compounds represent a new frontier of antimicrobial molecules, and the marine ecosystem represents a new challenge in this regard. In the present work, we evaluated the possibility of changes in the antibacterial activity of protamine-like (PL) proteins, the major nuclear basic [...] Read more.
Natural bioactive compounds represent a new frontier of antimicrobial molecules, and the marine ecosystem represents a new challenge in this regard. In the present work, we evaluated the possibility of changes in the antibacterial activity of protamine-like (PL) proteins, the major nuclear basic protein components of Mytilus galloprovincialis sperm chromatin, after the exposure of mussels to subtoxic doses of chromium (VI) (1, 10, and 100 nM) and mercury (1, 10, and 100 pM) HgCl2, since these metals affect some properties of PL. After exposure, we analyzed the electrophoretic pattern of PLs by both acetic acid-urea polyacrylamide gel electrophoresis (AU-PAGE) and SDS-PAGE and determined the MIC and MBC of these proteins on different gram+ and gram– bacteria. PLs, particularly after mussels were exposed to the highest doses of chromium and mercury, showed significantly reduced antibacterial activity. Just at the highest doses of exposure to the two metals, changes were found in the electrophoretic pattern of PLs, suggesting that there were conformational changes in these proteins, which were confirmed by the fluorescence measurements of PLs. These results provide the first evidence of a reduction in the antibacterial activity of these proteins following the exposure of mussels to these metals. Based on the results, hypothetical molecular mechanisms that could explain the decrease in the antibacterial activity of PLs are discussed. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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16 pages, 3804 KiB  
Article
Anti-Adipogenic Activity of Secondary Metabolites Isolated from Smilax sieboldii Miq. on 3T3-L1 Adipocytes
by Yeon Woo Jung, Jung A Lee, Ji Eun Lee, Hanna Cha, Yun-Hyeok Choi, Wonsik Jeong, Chun Whan Choi, Joa Sub Oh, Eun-Kyung Ahn and Seong Su Hong
Int. J. Mol. Sci. 2023, 24(10), 8866; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24108866 - 16 May 2023
Cited by 2 | Viewed by 1554
Abstract
Smilax sieboldii, a climbing tree belonging to Smilacaceae, has been used in traditional oriental medicine for treating arthritis, tumors, leprosy, psoriasis, and lumbago. To evaluate the anti-obesity effects of S. sieboldii (Smilacaceae), we screened methylene chloride (CH2Cl2), ethyl [...] Read more.
Smilax sieboldii, a climbing tree belonging to Smilacaceae, has been used in traditional oriental medicine for treating arthritis, tumors, leprosy, psoriasis, and lumbago. To evaluate the anti-obesity effects of S. sieboldii (Smilacaceae), we screened methylene chloride (CH2Cl2), ethyl acetate (EtOAc), aqueous-saturated n-butanol, and ethanol (EtOH) extracts of the whole plant at various concentrations to inhibit adipogenesis in adipocytes. The 3T3-L1 cell line with Oil red O staining with the help of fluorometry was used as an indicator of anti-obesity activity. Bioactivity-guided fractionation of the EtOH extract and subsequent phytochemical investigation of the active CH2Cl2- and EtOAc-soluble fractions resulted in the isolation of 19 secondary metabolites (1–19), including a new α-hydroxy acid derivative (16) and two new lanostane-type triterpenoids (17 and 18). The structures of these compounds were characterized using various spectroscopic methods. All the isolated compounds were screened for adipogenesis inhibition at a concentration of 100 μM. Of these, compounds 1, 2, 4–9, 15, and 19 significantly reduced fat accumulation in 3T3-L1 adipocytes, especially compounds 4, 7, 9, and 19, showing 37.05 ± 0.95, 8.60 ± 0.41 15.82 ± 1.23, and 17.73 ± 1.28% lipid content, respectively, at a concentration of 100 μM. These findings provide experimental evidence that isolates from S. sieboldii extracts exert beneficial effects regarding the regulation of adipocyte differentiation. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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Review

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23 pages, 1650 KiB  
Review
Metabolic Insights into Caffeine’s Anti-Adipogenic Effects: An Exploration through Intestinal Microbiota Modulation in Obesity
by Isabela Monique Fortunato, Quélita Cristina Pereira, Fabricio de Sousa Oliveira, Marisa Claudia Alvarez, Tanila Wood dos Santos and Marcelo Lima Ribeiro
Int. J. Mol. Sci. 2024, 25(3), 1803; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25031803 - 02 Feb 2024
Viewed by 1293
Abstract
Obesity, a chronic condition marked by the excessive accumulation of adipose tissue, not only affects individual well-being but also significantly inflates healthcare costs. The physiological excess of fat manifests as triglyceride (TG) deposition within adipose tissue, with white adipose tissue (WAT) expansion via [...] Read more.
Obesity, a chronic condition marked by the excessive accumulation of adipose tissue, not only affects individual well-being but also significantly inflates healthcare costs. The physiological excess of fat manifests as triglyceride (TG) deposition within adipose tissue, with white adipose tissue (WAT) expansion via adipocyte hyperplasia being a key adipogenesis mechanism. As efforts intensify to address this global health crisis, understanding the complex interplay of contributing factors becomes critical for effective public health interventions and improved patient outcomes. In this context, gut microbiota-derived metabolites play an important role in orchestrating obesity modulation. Microbial lipopolysaccharides (LPS), secondary bile acids (BA), short-chain fatty acids (SCFAs), and trimethylamine (TMA) are the main intestinal metabolites in dyslipidemic states. Emerging evidence highlights the microbiota’s substantial role in influencing host metabolism and subsequent health outcomes, presenting new avenues for therapeutic strategies, including polyphenol-based manipulations of these microbial populations. Among various agents, caffeine emerges as a potent modulator of metabolic pathways, exhibiting anti-inflammatory, antioxidant, and obesity-mitigating properties. Notably, caffeine’s anti-adipogenic potential, attributed to the downregulation of key adipogenesis regulators, has been established. Recent findings further indicate that caffeine’s influence on obesity may be mediated through alterations in the gut microbiota and its metabolic byproducts. Therefore, the present review summarizes the anti-adipogenic effect of caffeine in modulating obesity through the intestinal microbiota and its metabolites. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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27 pages, 2425 KiB  
Review
Insights into How Plant-Derived Extracts and Compounds Can Help in the Prevention and Treatment of Keloid Disease: Established and Emerging Therapeutic Targets
by Yong Chool Boo
Int. J. Mol. Sci. 2024, 25(2), 1235; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25021235 - 19 Jan 2024
Cited by 1 | Viewed by 1194
Abstract
Keloid is a disease in which fibroblasts abnormally proliferate and synthesize excessive amounts of extracellular matrix, including collagen and fibronectin, during the healing process of skin wounds, causing larger scars that exceed the boundaries of the original wound. Currently, surgical excision, cryotherapy, radiation, [...] Read more.
Keloid is a disease in which fibroblasts abnormally proliferate and synthesize excessive amounts of extracellular matrix, including collagen and fibronectin, during the healing process of skin wounds, causing larger scars that exceed the boundaries of the original wound. Currently, surgical excision, cryotherapy, radiation, laser treatment, photodynamic therapy, pressure therapy, silicone gel sheeting, and pharmacotherapy are used alone or in combinations to treat this disease, but the outcomes are usually unsatisfactory. The purpose of this review is to examine whether natural products can help treat keloid disease. I introduce well-established therapeutic targets for this disease and various other emerging therapeutic targets that have been proposed based on the phenotypic difference between keloid-derived fibroblasts (KFs) and normal epidermal fibroblasts (NFs). We then present recent studies on the biological effects of various plant-derived extracts and compounds on KFs and NFs. Associated ex vivo, in vivo, and clinical studies are also presented. Finally, we discuss the mechanisms of action of the plant-derived extracts and compounds, the pros and cons, and the future tasks for natural product-based therapy for keloid disease, as compared with existing other therapies. Extracts of Astragalus membranaceus, Salvia miltiorrhiza, Aneilema keisak, Galla Chinensis, Lycium chinense, Physalis angulate, Allium sepa, and Camellia sinensis appear to modulate cell proliferation, migration, and/or extracellular matrix (ECM) production in KFs, supporting their therapeutic potential. Various phenolic compounds, terpenoids, alkaloids, and other plant-derived compounds could modulate different cell signaling pathways associated with the pathogenesis of keloids. For now, many studies are limited to in vitro experiments; additional research and development are needed to proceed to clinical trials. Many emerging therapeutic targets could accelerate the discovery of plant-derived substances for the prevention and treatment of keloid disease. I hope that this review will bridge past, present, and future research on this subject and provide insight into new therapeutic targets and pharmaceuticals, aiming for effective keloid treatment. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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12 pages, 2252 KiB  
Review
Therapeutic Potential of Resveratrol for Glioma: A Systematic Review and Meta-Analysis of Animal Model Studies
by Ângelo Luís, Helena Marcelino, Fernanda Domingues, Luísa Pereira and José Francisco Cascalheira
Int. J. Mol. Sci. 2023, 24(23), 16597; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242316597 - 22 Nov 2023
Cited by 2 | Viewed by 1079
Abstract
Gliomas are aggressive malignant brain tumors, with poor prognosis despite available therapies, raising the necessity for finding new compounds with therapeutic action. Numerous preclinical investigations evaluating resveratrol’s anti-tumor impact in animal models of glioma have been reported; however, the variety of experimental circumstances [...] Read more.
Gliomas are aggressive malignant brain tumors, with poor prognosis despite available therapies, raising the necessity for finding new compounds with therapeutic action. Numerous preclinical investigations evaluating resveratrol’s anti-tumor impact in animal models of glioma have been reported; however, the variety of experimental circumstances and results have prevented conclusive findings about resveratrol’s effectiveness. Several databases were searched during May 2023, ten publications were identified, satisfying the inclusion criteria, that assess the effects of resveratrol in murine glioma-bearing xenografts. To determine the efficacy of resveratrol, tumor volume and animal counts were retrieved, and the data were then subjected to a random effects meta-analysis. The influence of different experimental conditions and publication bias on resveratrol efficacy were evaluated. Comparing treated to untreated groups, resveratrol administration decreased the tumor volume. Overall, the effect’s weighted standardized difference in means was −2.046 (95%CI: −3.156 to −0.936; p-value < 0.001). The efficacy of the treatment was observed for animals inoculated with both human glioblastoma or rat glioma cells and for different modes of resveratrol administration. The combined administration of resveratrol and temozolomide was more effective than temozolomide alone. Reducing publication bias did not change the effectiveness of resveratrol treatment. The findings suggest that resveratrol slows the development of tumors in animal glioma models. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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17 pages, 1593 KiB  
Review
Omega-3 Lipid Mediators: Modulation of the M1/M2 Macrophage Phenotype and Its Protective Role in Chronic Liver Diseases
by Luis Alberto Videla, Rodrigo Valenzuela, Andrea Del Campo and Jessica Zúñiga-Hernández
Int. J. Mol. Sci. 2023, 24(21), 15528; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242115528 - 24 Oct 2023
Viewed by 2209
Abstract
The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis and progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have brought in attention due to their potential to modulate inflammation and exert protective effects in various [...] Read more.
The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis and progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have brought in attention due to their potential to modulate inflammation and exert protective effects in various pathological conditions. Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown promise in mitigating inflammation and enhancing the resolution of inflammatory responses. They influence the M1/M2 macrophage phenotype balance, promoting a shift towards the M2 anti-inflammatory phenotype. Specialized pro-resolving mediators (SPMs), such as resolvins (Rvs), protectins (PDs), and maresins (MaRs), have emerged as potent regulators of inflammation and macrophage polarization. They show anti-inflammatory and pro-resolving properties, by modulating the expression of cytokines, facilitate the phagocytosis of apoptotic cells, and promote tissue repair. MaR1, in particular, has demonstrated significant hepatoprotective effects by promoting M2 macrophage polarization, reducing oxidative stress, and inhibiting key inflammatory pathways such as NF-κB. In the context of CLDs, such as nonalcoholic fatty liver disease (NAFLD) and cirrhosis, omega-3s and their SPMs have shown promise in attenuating liver injury, promoting tissue regeneration, and modulating macrophage phenotypes. The aim of this article was to analyze the emerging role of omega-3 FAs and their SPMs in the context of macrophage polarization, with special interest in the mechanisms underlying their effects and their interactions with other cell types within the liver microenvironment, focused on CLDs and the development of novel therapeutic strategies. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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19 pages, 2851 KiB  
Review
Chios Mastic Gum: Chemical Profile and Pharmacological Properties in Inflammatory Bowel Disease: From the Past to the Future
by Roberta Ottria, Ornella Xynomilakis, Silvana Casati, Ezio Abbiati, Giovanni Maconi and Pierangela Ciuffreda
Int. J. Mol. Sci. 2023, 24(15), 12038; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241512038 - 27 Jul 2023
Viewed by 2182
Abstract
Chios mastic gum, the product of the tree Pistacia lentiscus var. Chia, has been used for more than 2500 years in traditional Greek medicine for treating several diseases, thanks to the anti-inflammatory and antioxidant properties of its components. Despite the long-time use [...] Read more.
Chios mastic gum, the product of the tree Pistacia lentiscus var. Chia, has been used for more than 2500 years in traditional Greek medicine for treating several diseases, thanks to the anti-inflammatory and antioxidant properties of its components. Despite the long-time use of mastic in gastroenterology and in particular in chronic-inflammation-associated diseases, to date, the literature lacks reviews regarding this topic. The aim of the present work is to summarize available data on the effects of P. lentiscus on inflammatory bowel disease. A comprehensive review of this topic could drive researchers to conduct future studies aimed at deeply investigating P. lentiscus effects and hypothesizing a mechanism of action. The present review, indeed, schematizes the possible bioactive components of mastic gum. Particular care is given to P. lentiscus var. Chia medicaments’ and supplements’ chemical compositions and their pharmacological action in inflammatory bowel disease. Full article
(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 2.0)
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